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PCR RESULTS

Hello, I'm new to the site after finding some info on here I thought I would contribute by asking questions and hopefully answer any that anybody else has.

I was diagnosed with CML Oct 2011 at the Christie Unit at Oldham, Greater Manchester. I was very poorly losing about 20 pounds and a huge spleen.

I was only 35 years old and had always looked after myself.

Anyway things were going fine on Glivec until about April 2013 when my PCR results went from 1.2% to 1.6% and up to 2%.

In May I started on Nilotinib and so far so good, my results after 2 months went to 1% and then 3 months later 0.6%.

My last test from Oct has now showed 0.007 which I think is 0.7 %.

My question is, should I be worried after what happened on Glivec or is it such a small change that could be attributed to external factors.

Also struggling to understand the PCR wording. Is the result 0.007 or is it 0.7 %.

Does this mean that in every 100 ok cells there are 0.7 bad ones to put it simply.

Your help is appreciated.

Neil

I am also new to this business. But I am sure that if it is on International scale .007 is a great number congratulations

For my academic purpose do you mind giving the following info ?

1. What was your first WBC and Platelet reading at the time of diagnosis ?
2. What was your first PCR % ?
3. Have you ever achieved .1% ( MMR ) while on Gleevec ?
4. From the side effects point of view which TKI is better for you ?

Thomas

I can find out for you but not until my next appointment, I don't have the numbers to hand but know the WBC was in the thousands.

On Glivec the lowest I ever got was 1.2% after approx 18 months, it then started going to 1.6% and then 1.8% over a period of 6-8months.With regards to the side effects, the Nilotinib wins hands down.

I had upset stomach and aching joints and also watery eyes affecting my vision on Glivec.On Nilotinib I only have dehydration and slighlty higher liver functions test.No upset stomach or anything else, just a bit of a headache every now and again. Don't know if this is the tablets or not.

Can you help me understand the PCR results.

I went last week to see the specialist and the results showed 0.6% last time and then 0.7% in October. In brackets it shows (0.006) and then (0.007) with the percentage next to them.

Which number is referred to in the discussion on this board and should I be looking at getting to the 0.001 number or below?

Also should I be worried that the percentage has risen slightly or does this amount seem a little insignificant?

Hello Neil,

I'll hopefully try and answer some of your questions:

your response to Gleevec appeared to be sub-optimal and the upward tick was a cause for review as you effectively never achieved cytogenetic response. Per the ELN guidelines your doctor was right to change your TKI. As for what this means on Tasigna - probably not a lot. The efficacy of the 2nd generation TKIs is one of the reasons it is approved by NICE - it does have demonstrable efficacy for people who lose response on Gleevec. I would not be overly worried about the previous upward trend now you are on a different drug; having said that, i completely understand your anxiety about seeing a fractional rise between two PCR tests on Tasigna.

As for your current PCR test results: 0.6% is obviously much better than the ~1.8% you had on Gleevec before changing. The 'rise' to 0.7% is nothing abnormal as the PCR test can be affected by several factors and the result can vary by up to 0.5 log (error) - this is why absolute numbers are less important than overall long term trends. I bounce around between 0.04% and 0.15% with no real cause for concern one test to the next. Looking at the response you appear to be making progress; like me you may be a 'plodder' - it may take time for your numbers to drop, but a stable response around the MMR 0.1% level is a solid target to aim for in line with european leukaemia guidelines. Try not to worry about a 0.1% rise, look at the trend over time. Ideally we would all like to be down at MMR 5, which is 0.001%, but we won't all get that low with the current available TKIs.

When you switched TKIs did your doc run a mutation analysis? You should ask if this was undertaken - if not push your doc to have one done as at least then you can rule out any other factors. Again, do not worry if you do have a mutation as there are TKIs to address the majority of mutations.

Always ask your doc to give your PCR result in %International Standard. This removes any ambiguity and we (patients and health professionals) typically discuss results in %IS. What did your doctor say about the change from 0.6% to 0.7%?

Headaches are common on tasigna - i find drinking lots of water helps.

Also, even if Tasigna does not work, there is always sprycel (dasatinib) which is available through the cancer drugs fund. There are also 2 other TKIs are out there as well, but these are in their infancy.

In summary, a 0.1% change is not a 'rise' so to speak and could very easily be due to other factors such as sample quality; remember 2 data points do not make a trend. You have now reached Complete Cytogenetic Response, which is one of the most significant treatment milestones. Tasigna is an excellent drug and has demonstrable efficacy where patients have previously had sub-optimal results on Gleevec. I know it's an anxious time, but it's a marathon not a sprint and, on the current drug, the numbers suggest you're doing ok on your march towards MMR.

Chris

Chris has given you good advice. I would say that you need to ask your doctor if he/she is reporting your PCR results according to the IS(international scale)...depending on where you're are being treated I suspect not. You might be able to ask for the labs conversion factor so that you can convert the 0.7% result(your latest one and in my view not significantly different from the previous on at 0.6%) to tally with the IS.

For example:
In order to convert a given local labs qRT-PCR result to the international scale, it is necessary to calculate a conversion factor (CF)for that lab, which can be done as follows:

Given that 0.1% is agreed as MMR (or 3 log reduction) on the international scale (IS)

To find a local lab's Conversion Factor you need to divide 0.1%(MMR IS) by MMREq (whatever MMR value is at the local lab)

Once calculated it can be used to convert all that particular labs qRT_PCR results to the International Scale.

However, even if the lab has already calculated a conversion factor, not all doctors report PCR results on the IS to their patients. You will need to discuss this with your doctor.

From what you say, you are responding very well to nilotinib (Tasigna) after reaching a response 'plateau' on imatinib (Glivec). As Chris has already said, your doctor was right to change your therapy to a second generation TKI.... and it is obvious that the side effects are much less for you.

Your goal for now would be to get down to MMR (0.1% IS). When you reach this, then you can start to think about getting lower- some do, but a lot of patients do not or they take a long time to get down any further - as Chris says, this is a marathon not a sprint.

I hope this has not confused you further. Best to ask your doctor about how your PCR results are currently reported... IS or Local value?

Remember also that any given blood or marrow sample must contain an adequate number of control gene transcripts if you are to get a significant result. To report MMR there must be at least 10,000 control gene transcripts (ie. normal genes such as ABL or BCR)this way they can calculate the ratio of normal to abnormal (BCR-ABL1)transcripts in a sample.

Best wishes,
Sandy

Sorry for the delay in answering back, a very busy time working shifts at work. The doctor says that I should not worry about the result and I have already sent another sample for testing which should be back in about 3 weeks.

He basically told me to stop worrying about my levels and live life, he tries to be blunt and tell me off for worrying. He said that everything looks ok and that I shouldn't worry and that with the current medication around now and in the near future things will be ok.

I will ask about the results and if they are in IS and also about the mutation tests.
I don't have an appointment for another 2-3 months though so will have to wait a while.

Thanks for explaining a few things to me.